Satiety inducing composition

ABSTRACT

The invention provides the use of a whey protein and/or whey protein hydrolysate which stimulate the cellular release of the satiety peptides choleocystokinin and glucagon-like-peptide in the preparation of edible compositions. The edible compositions can be used to control body weight and have beneficial effects on satiety. Edible compositions are also provided.

FIELD OF THE INVENTION

The present invention relates to the use of certain whey proteins andwhey protein hydrolysates in the preparation of an edible compositionfor enhancing satiety in humans or animals. It also relates to a methodof controlling body weight using these whey proteins and whey proteinhydrolysates and to an edible composition comprising them.

BACKGROUND OF THE INVENTION

The incidence of obesity and the number of people considered overweightin countries where a so-called Western diet is adopted has increasedover the last decade. Since obesity and being overweight are associatedwith a variety of diseases such as heart disease, hypertension andarthereosclerosis, this increase is a major health concern. Furthermore,being overweight is considered by the majority of the Western populationas unattractive.

This has led to an increasing interest by consumers in their health andhas created a demand for products which help to reduce or control dailycaloric intake and/or control body weight and/or bodily appearance.Preferably, such products can be added to ordinary foodstuffs, or theycan be consumed prior to, during, after or instead of an ordinary meal.Consuming such a composition should, ideally, increase and/or prolongthe feeling of satiety for the consumer and/or extend the time intervalbetween meals and/or reduce the amount of calories consumed in asubsequent meal.

Recognising the demand for efficient and convenient satiety-inducingproducts, research has been carried out to find compounds that stimulatethe release of certain peptides associated with signaling, or causing,the feeling of satiety. These peptides are referred herein as “satietypeptides”. Such satiety peptides include, for example, cholecystokinin(CCK), enterostatin, somatostatin, amylin and glucagon-like-peptides(GLP), such as glucagon-like-peptide-1 (GLP-1).

Although a great number of molecules or compositions have been suggestedto be active in stimulating the release of one of the aforementionedsatiety peptides, only very few of them have been derived from naturalproducts and/or can be used in food products.

U.S. Pat. No. 6,207,638 discloses a nutritional composition stimulatingthe release of CCK, the composition comprising a) a protein selectedfrom casein, whey and soy, b) a glycomacropeptide, c) a long chain fattyacid, and d) soluble and insoluble fibers. Whey protein hydrolysates arenot disclosed and no teaching is given of the release of both CCK andglucagon-like-peptides by the whey protein.

WO 01/37850 discloses a milk protein hydrolysate inducing the release ofglucagon-like-peptide 1 (GLP-1). Caseino-glycomacropeptide has not beenfound to stimulate the cellular release of CCK.

WO 02/15719 discloses nutritional compositions comprising hydrolysedwhey proteins to provide reduced satiety effects from the compositions.The nutritional compositions are intended for people suffering fromreduced appetite such as those convalescing and anorexia suffers.

WO 99/49741 discloses a method for providing glutamine to a patient inneed thereof. The glutamine may be provided by a whey protein or a wheyprotein hydrolysate. Hydrolysed sweet whey may be used but no furtherdetails are given of suitable types.

US 2002/0044988 discloses compositions and methods that stimulate bodyprotein synthesis to improve muscle mass maintenance and recovery. Wheyprotein hydrolysates may be used in the compositions.

EP-A-1 201 137 discloses a method of preparation of cysteine/glycinerich peptides. Hydrolysed whey protein isolates are disclosed.

EP-A-1 034 704 discloses enteral nutritional compositions that maycomprise hydrolysates of milk proteins.

WO 01/43563 discloses milk protein hydrolysates for use in compositionsto be used to reduce the epidemiologically established risk of diabetesmellitus type I.

Whey based energy drinks are also known in the art. Designer WheyProtein Blast drinks (ex Next Proteins, California, USA) comprisesβ-lactoglobulin and α-lactalbumin and are used as food supplements forbuilding muscle mass. The drinks comprise very low levels ofcarbohydrates and no fat and thus the calories are providedpredominantly from the protein. A bottle of 20 American ounces (about600 ml) of the drink comprises no fat, 1 g carbohydrate and 17 gprotein. The drinks are expressly instructed not to be used for weightreduction.

Powders to produce drinks comprising β-lactoglobulin and α-lactalbumin,and such drinks, are known for blood pressure lowering applications. Apowder produced by Davisco Foods International (Minnesota, USA)comprises 20 g of β-lactoglobulin and α-lactalbumin, 1 g of fat and 6 gof carbohydrate per 30 g of powdered product. The powders can be mixedwith water or milk to produce the drink. No disclosure is made of use insatiety control applications. The powders and drinks provide over 55% ofthe total calories in the powder or drink (when made with water or cow'smilk) from the protein content.

However, despite the above developments, there is still a need in theart for edible compositions which provide a good satiety effect forconsumers, especially those wishing to control their calorie intakeand/or body weight. Furthermore, there is a need to provide suchproducts which help with the adherence to a dietary programme,especially a calorie controlled diet or with otherwise controllingcalorie intake. There is also a need for edible compositions which canbe used to help improve or control perception of body image or bodyweight.

In particular, there is a need for edible compositions which provide animproved satiety effect compared to conventional food products orconventional diet/meal replacement products. There is also a need toprovide edible compositions which have an acceptable taste as well asproviding good satiety effects, e.g. the products are not too sweet,nor, too bitter.

In particular, there is a need for meal replacement products whichprovide one or more of the above effects and/or advantages.

The present invention seeks to address one or more of theabove-mentioned problems.

In particular, it is an object of the invention to provide ediblecompositions which have a good satiety effect.

It is also an object of the invention to provide edible compositionswhich have an improved satiety effect compared to conventional foodproducts or to conventional diet/meal replacement products.

It is also an object of the invention to provide a method to help theconsumer to comply with a dietary plan, to control body weight and/or toimprove or maintain the perception of body image.

SUMMARY OF THE INVENTION

Surprisingly, it has now been found that certain whey proteins (WP)and/or whey protein hydrolysates (WPH) provide an improved satietyeffect. Without wishing to be bound by theory, it is believed that thisoccurs because they stimulate the cellular release of more than onesatiety peptide.

It has been found that WP and WPH that stimulate the cellular release ofboth satiety peptides cholecystokinin (CCK) and glucagon-like-peptides(GLP), especially glucagon-like-peptide-1 (GLP-1) are particularlyeffective in inducing satiety. Such WP and WPH increase the satietyeffects experienced by a person after eating an edible compositioncomprising them. It is believed that the combined release (eithersimultaneously or stepwise) of these two satiety peptides results in anenhanced feeling of satiety.

An enhanced feeling of satiety as referred to herein means a morepronounced and/or quicker feeling of satiety (satiation) and/or a longerlasting feeling of satiety after eating (satiety). Such effectstypically extend the time elapsed between meals and can result in asmaller amount of food and/or number of calories being consumed dailyetc. The references herein to satiety include both what is strictlyreferred to as “satiation” and “satiety”, including “end-of-meal”satiety and “between-meals” satiety.

It is believed that the cellular release of CCK in the body isassociated with the feeling of satiety that occurs at the end of a meal(end-of-meal satiety) whereas the cellular release of GLP is associatedwith the feeling of satiety that lasts after eating (between-mealssatiety). Thus, CCK release is believed to be involved in signaling tothe body when a person has eaten enough of a meal and GLP is believed tobe involved in signaling to the body that we are still satiated from aprevious meal.

It has also been found that the WP and WPH of the present inventionexhibit an increased level of induced cellular GLP release at a givenconcentration than do other milk proteins, milk protein hydrolysates ornon-hydrolysated whey proteins.

According to a first aspect, the present invention provides the use of awhey protein and/or whey protein hydrolysate in an edible composition,the whey protein and/or whey protein hydrolysate being able to inducethe cellular release of glucagon-like-peptides and cholecystokinins,wherein the whey protein and/or whey protein hydrolysate on or afterconsumption of the edible composition induces an enhanced feeling ofsatiety.

The term “an enhanced feeling of satiety” as used herein refers to thefeeling of satiety obtained upon consumption of the edible compositionsof the invention compared to the feeling of satiety obtained after theconsumption of an edible composition which is of substantiallyequivalent caloric and macro-nutrient content but wherein the wheyprotein and/or whey protein hydrolysate is replaced by the equivalentamount of cow's milk protein.

The edible compositions of the present invention are intended forconsumption by a human or animal.

According to a second aspect, the present invention provides the use ofa whey protein and/or whey protein hydrolysate in an edible composition,the whey protein and/or whey protein hydrolysate being able to inducethe cellular release of glucagon-like-peptides and cholecystokinins andwherein the composition is used to improve or control perception of bodyimage, and/or to control body weight, and/or to control calorie intakeand/or help adherence to a dietary plan.

According to a third aspect, the present invention provides a method forinducing satiety in a human or animal, the method comprising the step ofadministering to a human or animal by means of an edible composition, aneffective amount of a whey protein and/or whey protein hydrolysate whichis capable of inducing the cellular release of glucagon-like peptidesand cholecystokinins.

According to a fourth aspect, the present invention provides a methodfor improving or controlling perception of body image, and/orcontrolling body weight, and/or controlling calorie intake and/orhelping adherence to a dietary plan, the method comprising the step ofadministering to a human or animal by means of an edible composition, aneffective amount of a whey protein and/or whey protein hydrolysate whichis capable of inducing the cellular release of glucagon-like peptidesand cholecystokinins.

According to a further aspect, the present invention provides a liquidor flowable edible composition comprising protein, wherein the proteincomprises 0.1 to 50% by weight based on the weight of the composition ofa whey protein hydrolysate capable of inducing the cellular releaseglucagon-like-peptides and cholecystokinins, and wherein 50% or less ofthe total calories in the edible composition are provided by theprotein.

A “flowable” product as referred to herein is a liquid, semi-liquid,powdered or particulate product which when poured with or without theapplication of pressure flows out of a container even if the productdoes not flow out in a continuous stream. The term does not includeproducts which are in one piece (e.g. have a shaped solid form such asblocks, cubes etc) as these are not capable of flowing, nor, productswhich are eaten in a physical state which does not flow such asice-cream.

The liquid or flowable edible compositions of the invention give goodsatiety effects, acceptable sensory properties (such as acceptabletaste) and have a good balance of the level of whey protein and/or wheyprotein hydrolysate used and the percentage of calories in the productobtained from the total amount of protein in the composition. Thiscombination is especially suitable for a meal replacement product.

According to a further aspect, the present invention provides a liquidor flowable edible composition 0.1 to 80% by weight based on the weightof the composition of a whey protein hydrolysate capable of inducing thecellular release glucagon-like-peptides and cholecystokinins, andwherein the composition further comprises added vitamins and/or mineralsselected from at least one of vitamins A, B1, B2, B3, B5, B6, B11, B12,biotin, C, D, E, H, and K and calcium, magnesium, potassium, zinc andiron.

According to a further aspect, the present invention provides an ediblecomposition in the form of a bar and comprising a total amount of from0.1 to 80% by weight based on the weight of the composition ofhydrolysates of β-lactoglobulin, α-lactalbumin or a mixture thereof.

In all of the above aspects of the invention whey protein hydrolysatesare preferred. The preferred whey protein hydrolysates comprisehydrolysates of β-lactoglobulin, α-lactalbumin or a mixture thereof.

The use of the WP and/or WPH which induce the cellular release of bothCCK and GLP in the preparation of edible compositions is advantageous interms of the satiety effect obtained from the consumption of thatproduct, compared to the use of ingredients which only induce therelease of either CCK or GLP.

The advantages of the present invention include greater efficacy of thesatiety effect; for example an enhanced feeling of satiety, feelingsatiated sooner whilst eating and/or remaining satiated for a longerperiod of time after eating. These advantages are especially beneficialfor the compliance with dietary plans or programmes and/or the controlor maintenance of body weight and/or body perception. There are alsolonger term advantages associated with helping in the prevention ofdiseases related to being overweight.

Except in the operating and comparative examples, or where otherwiseexplicitly indicated, all numbers in this description indicating amountsof material or conditions of reaction, physical properties of materialsand/or use are to be understood as modified by the word “about”. Allamounts are as percentages by weight unless otherwise stated. For theedible compositions, all percentages are by weight based on the totalweight of the composition unless otherwise stated.

The term “comprising” is meant not to be limiting to any subsequentlystated elements but rather to encompass non-specified elements of majoror minor functional importance. In other words the listed steps,elements or options need not be exhaustive. Whenever the words“including” or “having” are used, these terms are meant to be equivalentto “comprising” as defined above.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the concentration of GLP-1 secreted from GLUTaq cells intothe media after 2 hours incubation at 37° C. with the Biozate 1.

FIG. 2 shows the concentration of CCK secreted from GLUTaq cells intothe media after 1 hour incubation at 37° C. with Biozate 1.

On both FIG. 1 and 2, the x axis shows the series and the concentrationof Biozate 1 used. The y axes of FIG. 1 and 2 show the concentration ofGLP-1 or CCK secreted from GLUTaq cells into the media after incubation.For FIG. 1 the concentration is expressed in pico moles per liter(10⁻¹²M) and for FIG. 2 in nanograms/ml.

DETAILED DESCRIPTION

Satiety Peptides

Cholecystokinin(s) and “CCK” as used herein include all peptides of theCCK family, including (but not limited to); CCK-4, CCK-8, CCK-22,CCK-23, CCK-24, CCH-25, CCK-36, CCK-27, CCK-28, CCK-29, CCK-30, CCK-31,CCK-32, CCK-33, CCK-39, CCK-58.

Glucagon-like-peptides (GLP) and “GLP” as used herein include allpeptides of the GLP family including (but not limited to); GLP-1 andGLP-2. GLP-1 has been found to be especially of interest.

Additional satiety peptides may be cellularly released by using the WPand/or WPH according to the invention. Examples of such satiety peptidesinclude amylin, GRP-NMB, enterostatin, ApoA-IV, glucagon, somastatin,PYY, leptin and a variety of cytokines such as CNTF.

Cellular Release

Inducing the cellular release of the satiety peptides as describedherein refers to inducing the release thereof by suitable cells,preferably gastrointestinal cells, after the ingestion of the wheyprotein (WP) and/or whey protein hydrolysate (WPH) by those cells.

Inducing the cellular release of the satiety peptides according to theinvention can be measured in vitro, for example by the use of anintestinal cell line. Suitable cell lines are well known in the art. Thecells used in the examples are GLUTag cells which are an L cell linefrom intestinal endocrine tumors arising in the large bowel inproglucagon-simian virus 40 large T antigen transgenic mice. These cellsare commercially available and are further described in the publicationby Drucker D. J. et al (1994): Activation of proglucagon genetranscription by protein kinase A in a novel mouse enteroendocrine cellline. Mol Endocrinol 8:1646-1655.

Examples 1 and 2 further illustrate the in vitro cellular release of CCKand GLP-1. The information in these examples is incorporated byreference into this section.

Without wishing to be bound by theory, it is believed that when asubject (animal or human) ingests the claimed WP and/or WPH, either byitself or as part of an edible composition, the cellular release of CCKand GLP in the body is stimulated resulting in the satiety effect.

This cellular release can also be measured in vivo, for example, bymeasuring the increase or appearance of CCK and GLP levels in the bloodof that subject after consumption of the WP and/or WPH or an ediblecomposition comprising it. Suitable techniques for measuring the CCK andGLP levels in the blood are well known in the art and do not need to befurther described here.

The WP and/or WPH of the invention show cellular release of CCK andGLP-1 in the in vitro cellular release test of examples 1 and 2,particularly, when used at a concentration of at least 5 mg/ml.

Without wishing to be bound by theory, it is believed that the WP/WPH ofthe invention may provide enhanced satiety effects by at least one ofthe following mechanisms:

-   1) by triggering the release of CCK from the duodenal and jejunum    mucosal (I) cells and by triggering the release of GLP-1 from    mucosal L cells in the distal ileum and colon from processing of    major proglucagon fragment by prohormone convertase PCI/3.-   2) CCK-like peptides in the WP/WPH may activate CCK-A receptors on    the gastric pylorus causing contraction resulting in gastric    distension. Stomach distension activates receptors on the afferent    gastric vagus nerve, which then transmits signals via the nucleus    tractus solitarius (NTS) to the satiety centre of the hypothalamus.-   3) CCK-like peptides in the WP/WPH may bind to receptors present in    the area postema adjacent to the NTS at the base of the fourth    ventricle. The blood brain barrier overlying the fourth ventricle is    leaky and could permit passage of a relatively small peptide like    CCK.-   4) CCK-like peptides in the WP/WPH may also bind directly to    receptors on the afferent gastric vagus which could directly    transmit the information to the NTS.

The Whey Protein and Whey Protein Hydrolysate

The terms “whey protein and/or whey protein hydrolysate which is/arecapable of inducing the cellular release of glucagon-like-peptides andcholecystokinins”, “WP” and “WPH” as used herein include all of thefollowing; a single whey protein or whey protein hydrolysate whichinduces the cellular release of both the aforementioned satiety peptidesand a mixture of two or more whey proteins or whey protein hydrolysateswherein the mixture induces the cellular release of both peptides evenif at least one of the components induces the cellular release of onlyone of the peptides. References herein to WP and WPH are used to referto both the singular and the plural use of whey protein and whey proteinhydrolysate.

The WP may comprise any whey protein which is capable of inducing thecellular release of glucagon-like-peptides and cholecystokinins. The WPHmay comprise any hydrolysed whey protein that is capable of inducing thecellular release of glucagon-like-peptides and cholecystokinins.

Suitable methods of hydrolysis of the whey protein include chemicalprocesses (for example by acid hydrolysation) or enzymatical processes(including treatment with peptidases and bacterial or plant proteases)or by treatment with bacterial cultures. Examples of suitable enzymeswhich can be used to hydrolyse the WP include pepsin, trypsin andchymotrypsin.

It is especially preferred that the WPH comprises hydrolysates ofβ-lactoglobulin or α-lactalbumin, most preferably mixtures thereof. Theweight ratio of the β-lactoglobulin or α-lactalbumin hydrolysates in themixture is preferably in the range of from 5:1 to 1:5, more preferably4:1 to 1:4, such as 3.5:1 to 1:2.

One particular WPH which may be used comprises from 5 to 20% by weightof aspartic acid, 10 to 25% by weight of leucine, 5 to 20% by weight oflysine and 10 to 32% by weight of glutamic acids.

The WPH may have a degree of hydrolysis in the range of up to 20%,preferably of from 1 to 15%, more preferably of from 2 to 10%, such as 5to 9%. The degree of hydrolysis is determined by OPA methodology (Lee KS, Drescher D G., Fluorometric amino-acid analysis witho-phthaldialdehyde (OPA), Int. J. Biochem. 1978; 9(7): 457-467).

The WP and WPH preferably have a weight average molecular weight in therange of from about 1000 Dalton to 12000 Dalton, preferably of from 2000Dalton to 8000 Dalton. It is preferred that 4 to 40% by weight, morepreferably 10 to 30% of the WPH has a weight average molecular weight inthe rage of from 2000 to 5000 Daltons and/or 1 to 30% by weight, morepreferably 2 to 20% of the WPH has a weight average molecular weight inthe range of from 5000 to 10000 Daltons.

The WP and WPH preferably have a pH in the range of from 6 to 9 at 20°C. in a 10 mg/ml solution in de-ionised water, more preferably of from6.5 to 8.

WP and WPH according to the invention are known in the art and arecommercially available. A description for one method to obtain the WPHis described in WO 01/85984 A1. A suitable commercially available sourceof the WPH is the Biozate™ range of whey protein hydrolysate productsfrom Davisco Foods Inc, Minnesota, USA. The products designated “Biozate1, 3 and 5” have been found to be especially suitable.

The WP and/or WPH is/are used in the preparation of edible compositions.The term “preparation” as used herein includes all suitable techniquesof producing edible compositions, for example, mixing, blending,homogenising, high-pressure homogenising, emulsifying, dispersing,and/or encapsulating. The WP and/or WPH may be included in the ediblecomposition by any suitable method known in the art and these methodswill depend upon the type of edible composition.

The WP and/or WPH may be micro-filtered or ion-exchanged (either as thehydrolysate or as the parent protein). It may be enhanced withglutamine, alanine, cystine and branched chain amino acids.

Method of Administering the WP and/or WPH

The invention also provides the aforementioned methods for inducingsatiety in a human or animal, for improving or controlling perception ofbody image, for controlling body weight, for controlling calorie intakeand/or for helping adherence to a dietary plan, by administering aneffective amount of the WP and/or WPH.

Furthermore the invention provides a method for altering the rate ofgastric emptying, gastrointestinal (GI) transit and/or nutrient uptakefrom the GI cells of a human or animal, by administering to a human oranimal an effective amount of the WP and/or WPH of the invention.

The total effective amount of WP and/or WPH administered according tothe method may vary according to the needs of the person to whom it isadministered. Typically total amounts of from 0.1 g to 150 g will beadministered, preferably 1 g to 80 g, more preferably 5 g to 50 g perday. The effective daily amount may be administered by a single dose orby multiple doses.

The WP and/or WPH may be administered to the animal or human in anysuitable form, for example as a capsule, tablet, solution, or,preferably as part of an edible composition as described hereinincluding bar products and liquid products such as ready-to-drinkproducts.

The Edible Composition

The edible composition may be in the form of a nutritional compositionor supplement (such as a tablet, powder, capsule or liquid product), afood composition (product) such as a meal replacement product or abeverage.

A nutritional composition or supplement as used herein refers to acomposition or supplement which provides at least one biologicallybeneficial agent such as vitamins, minerals, trace elements, the WPH etcand which is intended to supplement the amount of such agents obtainedthrough normal dietary intake.

A food composition according to the invention may be any food which canbe formulated to comprise the WP and/or WPH and which also contains atleast one of protein, fat, and/or carbohydrate. It is preferred that thefood composition is one intended to be used in a weight loss or weightcontrol plan.

Such products typically have a controlled calorie content and are of alower calorie content than the equivalent ‘full calorie’ foodcomposition, for example, the so-called ‘diet’ or ‘low calorie’products. Examples include “low-calorie” drinks and “low-calorie” snackproducts such as bars. It is also preferred that the food composition isa meal replacement product.

Suitable food compositions according to any aspect of the invention maybe suitably selected from dairy based products (such as milk basedproducts and drinks), soy based products, breads and cereal basedproducts (including pasta and cereal bars), cakes, biscuits, spreads,oil-in-water emulsions (such as dressings and mayonnaise), ice creams,desserts, soups, powdered soup concentrates, sauces, powdered sauceconcentrates, beverages, sport drinks, health bars, fruit juices,confectionery, snack foods, ready-to-eat meal products, pre-packed mealproducts, and dried meal products etc.

A meal replacement product as referred to herein refers to a productwhich is intended to replace one or more conventional meals per day;they are of a controlled calorie content and are generally eaten as asingle product. Examples of meal replacement products include; liquidproducts such as milk or soya-based drinks, soluble powders used toprepare those drinks and drinks prepared therefrom, bars, soups, cerealor noodle or pasta-based products, desserts such as rice puddings,custards and the like. Meal replacement products are generally used byconsumers following a calorie controlled diet.

Meal replacement products are especially preferred according to thepresent invention. They have been found to provide good satiety effectscombined with restricted calorie content in a convenient form. It isespecially preferred that the meal replacement product is a ready todrink liquid, a liquid produced from a soluble powdered product, a soup,a dessert, a bar, a cereal based or pasta based or noodle based product,or, a soluble or dispersible powdered product.

The edible composition may be for example; a solid product, a powderedproduct, a tablet, a capsule, a liquid, a flowable, spoonable, pourableor spreadable product or a bar etc. The edible composition may be apowder which is mixed with a liquid, such as water or milk, to produce aliquid or slurry product (such as a meal replacement product).

The edible compositions comprise a total amount of from 0.1% to 80% byweight of the WP and/or WPH based on the weight of the composition,preferably 0.1 to 40 or 50% wt, more preferably 0.5 or 1 to 30% wt, mostpreferably 2 or 5 to 20% wt. The edible compositions preferably comprisean amount of from 0.1 to 80% by weight, preferably 1 to 50%, ofhydrolysates of β-lactoglobulin, α-lactalbumin or mixtures thereof basedon the weight of the composition.

According to one embodiment of the invention, the edible compositionsmay comprise less than 20 g in total per serving, or per product wherethe product is used as a single serving, of the WP and/or WPH whether ornot the above-mentioned amounts are used.

If the edible composition is a liquid or flowable composition, such asliquid meal replacement product or a soup, then the total amount of WPand/or WPH will preferably be in the range of from 0.1 to 40 or 50% byweight, more preferably 0.5 or 1 to 30% wt, most preferably 2 to 20% wtbased on the total weight of the composition.

According to one aspect of the invention, the edible composition is aliquid or flowable composition which comprises protein, wherein theprotein comprises 0.1 to 50% by weight based on the weight of thecomposition of WPH according to the invention and 50% or less of thetotal calories in the edible composition are provided by the totalprotein present in the composition (including the WPH). It is especiallypreferred that the composition comprises a total amount of from 0.5 to30% by weight based on the weight of the composition of the WPH and 40%or less of the total calories in the edible composition are provided bythe total protein present in the composition.

According to another aspect of the invention, the edible composition isa liquid or flowable composition comprising 0.1 to 80% by weight basedon the weight of the composition of WPH of the invention and furthercomprising added vitamins and/or minerals selected from at least one ofvitamins A, B1, B2, B3, B5, B6, B11, B12, biotin, C, D, E, H, K andcalcium, magnesium, potassium, zinc and iron.

If the edible composition is a bar or other solid product product suchas bar meal replacement product, then the amount of WP and/or WPH willtypically be in the range of from 0.1 to 80% by weight, preferably 0.1to 40% by weight based on the total weight of the composition. It isespecially preferred that the bar compositions comprise β-lactoglobulin,α-lactalbumin, or hydrolysates thereof, or a mixture thereof in a totalamount of from 0.1 to 80% by weight based on the weight of thecomposition. For the avoidance of doubt, such a composition does notinclude powdered or particulate compositions.

The edible composition will typically comprise protein in addition tothe WP and/or WPH. The total amount of protein in the composition ispreferably an amount of from 0.1 to 30 or 40% by weight of the ediblecomposition. It is preferred that the compositions comprise 0.5 to 25%wt of total protein, preferably 1 to 20% wt. In the liquid or flowablecompositions the protein present provides up to 50% of the totalcalories of the edible composition, more preferably between 20% and 50%,most preferably between 25% and 50%. For the other types of ediblecompositions, these amounts are preferred but are not essential.

The edible composition may comprise edible fats, preferably in an amountof up to 60 or 70% by weight based on the weight of the composition,more preferably from 0.5 to 30 or 35% wt, most preferably from 0.75 to10 or 20% fat. Any suitable fat may be used with vegetable fats beingespecially preferred for example, vegetable fats, plant oils, nut oils,seed oils, or mixtures thereof. Saturated or unsaturated(mono-unsaturated and poly-unsaturated) fats may be used.

The edible compositions may also comprise one or more carbohydrates,preferably in an amount of from 1 to 95% by weight based on the weightof the composition, more preferably 5 to 70% wt, most preferably 10 to60% wt, such as 15 to 50% wt.

Any suitable carbohydrate may be used, for example sucrose, lactose,glucose, fructose, corn syrup, maltodextrins, starch, modified starch ormixtures thereof.

The edible composition may also comprise dietary fibres, for example inan amount of from 0.1 to 40 or 50% by weight based on the weight of thecomposition, preferably 0.5 to 20% wt.

The edible composition may comprise dairy products such as milk,yoghurt, kefir, cheese or cream for example in an amount up to 70% byweight based on the weight of the composition, preferably 1 to 50% wt.Alternatively the edible composition may be soy-protein based, with thesoy-protein used in the same amounts. The inclusion of these ingredientswill be chosen so that the desired amount of protein, fat andcarbohydrates etc are included in the edible composition.

The edible composition may comprise one or more emulsifiers. Anysuitable emulsifier may be used, for example lecithins, egg yolk,egg-derived emulsifiers, diacetyl tartaric esters of mono, di or triglycerides or mono, di, or triglycerides. The composition may comprisean amount of from 0.05 to 10% by weight, preferably from 0.5% to 5% wt,of the emulsifier based on the weight of the composition.

The edible composition may also comprise stabilisers. Any suitablestabiliser may be used, for example starches, modified starches,vegetable or microbial gums, pectins or gelatins. The composition maycomprise an amount of from 0.01 to 10% by weight, preferably 1 to 5% wtof stabiliser based on the weight of the composition.

The edible composition may comprise up to 60% by weight of fruit orvegetables pieces or particles, concentrates, juice or puree based onthe weight of the edible composition. Preferably the compositionscomprise 0.1 to 40% wt, more preferably 1 to 20% wt of theseingredients. The amount of these ingredients will depend upon the typeof edible composition; for example soups will typically comprise higherlevels of vegetables than will a milk based meal replacement drink.

The edible composition may also comprise 0.1 to 15% by weight of ediblesalts based on the weight of the composition, preferably 3 to 8% wt. Anyedible salts may be used, for example, sodium chloride, potassiumchloride, alkali metal or alkaline earth metal salts of citric acid,lactic acid, benzoic acid, ascorbic acid, or, mixtures thereof. Calciumsalts may also be used such as calcium chloride and calcium caseinate.

The edible composition may comprise one or more cholesterol loweringagents in conventional amounts. Any suitable, known, cholesterollowering agent may be used, for example isoflavones, phytosterols, soybean extracts, fish oil extracts, tea leaf extracts.

The edible composition may comprise up to 10 or 20% by weight, based onthe weight of the composition, of minor ingredients selected from addedvitamins, added minerals, herbs, spices, flavourings, aromas,antioxidants, colourants, preservatives or mixtures thereof. Preferablythe compositions comprise of from 0.5 to 15% by weight, more preferably2 to 10% of these ingredients. It is especially preferred that thecompositions comprise added vitamins and minerals. These may be added bythe use of vitamin premixes, mineral premixes and mixtures thereof.Alternatively the vitamins and/or minerals may be added individually.These added vitamins and/or minerals are preferably selected from atleast one of vitamins A, B1, B2, B3, B5, B6, B12, biotin, C, D, E, H, Kand calcium, magnesium, potassium, zinc and iron. Iodine, manganese,molybdenum, phosphorus, selenium and chromium may also be included.

The amounts of protein, fat, carbohydrate and other ingredients in theedible composition will vary according to the product format of thecomposition and also, where required, according to national or regionallegislation.

If the edible composition is a meal replacement product then the caloriecontent of the product is preferably in the range of from 50kilocalories (kcals) to 600 kcals, more preferably 100 kcals to 500kcals, most preferably 150 or 200 kcals to 400 kcals per serving of themeal replacement product.

The compositions may be made by any suitable method known in the art;such methods are well known to those skilled in the art and do not needto be described further here.

The edible composition may be consumed by a human or an animal inconnection with any one or more of the following; the treatment ofobesity or being overweight; to improve or maintain the perception ofbody image; aiding compliance with a dietary plan e.g. to control,reduce or maintain body weight; to extend the time elapsed betweenmeals; to control, maintain or reduce daily calorie intake; to suppressappetite.

The WP and/or WPH may be used in the preparation of an ediblecomposition, which composition (after consumption by a human or ananimal) induces a prolonged period for gastric emptying, or prolongedgastrointestinal (GI) transit or prolonged nutrient uptake from the GIcells compared to the consumption of a substantially nutritionallyequivalent composition not comprising the WP and/or WPH.

A nutrient as referred to herein may be any component of a food productfrom which the consumer derives physiological benefit. Examples includemacro-nutrients such as carbohydrates, fats and proteins ormicro-nutrients such as vitamins, minerals, and trace elements. Fibres,although not absorbed by the body, are considered herein as nutrients.Water, although it provides a benefit to the body, is not considered asa nutrient.

The consumption of a composition comprising the WP and/or WPH accordingto the invention may occur as a part of a dietary plan, such as thoseintended to reduce or control body weight. For example, a subjectfollowing that plan may be better able to reduce, control or maintaintheir body weight, e.g. by following the dietary plan for a longerperiod of time and/or adhering more closely to the plan as they feelless temptation to snack or over-eat. The term “dietary plan” as usedherein includes those for controlling body weight and those followed formedical reasons.

Another advantage of the present invention is that it provides methodsand compositions to treat obesity or alter gastric transit and nutrientuptake in the body, which compositions can be simply eaten rather thanneeding to be injected as occurs with some hormones used in thetreatment of obesity.

The invention is further described by way of the following exampleswhich are to be understood as not limiting. Further examples within thescope of the invention will be apparent to the person skilled in theart.

EXAMPLES Examples 1 and 2: Stimulated Release of GLP 1 and CCK inCultured GLUTag Cells

1. Materials

a) Whey Protein Hydrolysate:

The whey protein hydrolysate used was Biozate 1 which is a commerciallyavailable material from Davisco Foods International Inc., Le Sueur,Minn., U.S.A. Biozate 1 comprises a mixture of hydrolysedβ-lactoglobulin and α-lactalbumin.

The technical specification of Biozate 1 is given below. The pH is 8.0.The degree of hydrolysis, as measured by the OPA method referred tohereunder, is 5.5+/−1.5. The molecular weight profile (Daltons) is: 30to 45% greater than 10,000, 7 to 12% in the range 5000 to 10000, 15 to25% in the range 2000 to 5000, 30-45% less than 2000 as measured bySEC-HPLC.

b) GLUTag Cells:

The GLUTag cells were obtained under licence from Toronto GeneralHospital, Toronto, Canada. GLUTag cells are an L cell line fromintestinal endocrine tumors arising in the large bowel inproglucagon-simian virus 40 large T antigen transgenic mice. These cellsare further described in the publication by Drucker D. J. et al (1994):Activation of proglucagon gene transcription by protein kinase A in anovel mouse enteroendocrine cell line. Mol Endocrinol 8:1646-1655.

c) Materials for Cell Culture:

Dulbecco's Modified Eagles Medium (DMEM) and bovine serum (FBS) wereobtained from Invitrogen Ltd (Paisley, Scotland, UK).

2. Method

GLUTaq cells were grown during incubation at 37° C. in DMEM containing10% (vol/vol) FBS. The medium was changed every 3 to 4 days until cellconfluence was achieved. The cells were then trypsinized, plated in24-well cultures plates (0.5×10⁵ cells/well) and the plates were storedunder the same incubation conditions as described above. After 3 daysstorage the cells were washed twice with DMEM containing 0.5% (vol/vol)FBS and then, to four series (A to D) of 3 wells, different amounts ofBiozate 1 were added as detailed below. Thus, each series was preparedin triplicate. A control sample which did not have any added Biozate 1was also prepared in triplicate.

-   Series A—0.5 mg/ml Biozate 1-   Series B—3 mg/ml Biozate 1-   Series C—5 mg/ml Biozate 1-   Series D—10 mg/ml Biozate 1

The plates were incubated as detailed above and after incubation for 1hour an aliquot was taken from each plate to measure CCK release. Afurther aliquot was taken from each plate after 2 hours incubation tomeasure GLP-1 release. The aliquots were treated as detailed belowbefore being tested to determine CCK or GLP-1 release.

The aliquots were collected and 50 μg/ml phenylmethanesulfonyl fluoride(PMSF) was added thereto. The aliquots were frozen at −80° C. forsubsequent analysis for CCK and GLP-1 secretion. The aliquots weredefrosted and centrifuged (5000 g) to remove cell debris. The CCK andGLP-l release from the GLUTaq cells was then tested.

CCK release was measured using a commercial enzyme immunoassay kit (fromPhoenix Pharmaceuticals, Belmont, Calif., USA) which measures CCK 26-33non-sulfated and sulfated. According to the test kit specifications, theintra-assay variation is <5% and the inter-assay variation is <14%.

GLP-1 release was measured using a commercial ELISA kit (from LincoResearch Inc., St Charles, Mo., USA). This kit measures biologicallyactive forms of GLP-1 [i.e. GLP-1 (7-36 amide) and GLP-1 (7-37)]. Priorto measuring GLP-1 release, the aliquots were diluted 1 parts to 10parts with DMEM containing 0.5% (vol/vol) FBS to bring the GLP-1concentration within the standard detection range of the ELISA kit.

FIG. 1 shows the concentration of GLP-1 secreted from GLUTaq cells intothe media after 2 hours incubation at 37° C. with the Biozate 1.

FIG. 2 shows the concentration of CCK secreted from GLUTaq cells intothe media after 1 hour incubation at 37° C. with Biozate 1.

On both FIGS. 1 and 2, the x axis shows the series and the concentrationof Biozate 1 used. The y axes of FIGS. 1 and 2 show the concentration ofGLP-1 or CCK secreted from GLUTaq cells into the media after incubation.For FIG. 1 the concentration is expressed in pico moles per liter (10 M)and for FIG. 2 in nanograms/ml.

Cell viability was positively determined using the CytoTox 96^(R)non-radioactive cytotoxicity assay (Promega, Madison, USA) in order toprove that peptide release was not due to cell death.

From the results in FIGS. 1 and 2, it can be seen that the whey proteinhydrolysate used (a mixture of β-lactoglobulin and α-lactalbuminhydrolysates) results in the release of both GLP-1 and CCK from theGLUTaq cells into the media.

Example 3 Meal Replacement Bar Product

A meal replacement bar product comprising WPH may be prepared accordingto the formulation below.

Ingredient Percentage by weight Honey 16.0 Sucrose 10.0 Biozate 1 (WPH)13.0 Whey protein*¹ 13.0 Chopped dried fruit and nuts 10.0 Soy flour 5.0Peanut butter 5.0 Maltodextrin 4.0 Oats 6.0 Bran fibre 2.0 Flavourings2.0 Vitamin/mineral premix 2.0 Chocolate flavoured coating to 100% wt*¹not according to the present invention.

The bar is made by thoroughly mixing together the honey and maltodextrinwith the peanut butter. The remaining ingredients except the chocolateflavoured coating are added and the mixture is further mixed and formedinto a bar shape. To coat it the bar is passed through a curtain ofmolten chocolate flavoured coating. The bar is allowed to cool tosolidify the coating.

The edible composition shows good satiety effects compared to theequivalent composition wherein the whey protein hydrolysate is replacedby the same amount of cow's milk protein.

Example 4 Ready to Drink Liquid Meal Replacement Product

A meal replacement ready to drink liquid comprising WPH may be preparedaccording to the formulation below.

Ingredient Percentage by weight Water 75.5 Sucrose 2.0 Biozate 1 (WPH)5.0 Skimmed milk solids 2.0 High fructose corn syrup 8.0 Carageenan gum1.0 Vegetable oil 2.0 Caramel flavouring 1.5 Colourings, otherflavourings 1.0 Vitamin/mineral premix 2.0

The ingredients were added to the water and the composition was mixeduntil an homogenous product was obtained.

The edible composition shows good satiety effects compared to theequivalent composition wherein the whey protein hydrolysate is replacedby the same amount of cow's milk protein.

Example 5 Ice Tea Product

An ice tea product (concentrate) comprising WPH may be preparedaccording to the formulation below. The tea may be made by mixing theingredients together, with stirring, until a substantially homogenousproduct is obtained. The product may be cooled as desired.

Ingredient Percentage by weight Maltodextrin 39.4 Tea powder 9.0Aspartame 2.5 Peach flavour 3.6 N&A apricot flavour 1.2 Citric acid 9.0Magnesium oxide 0.2 Biozate 1 10.0 Vitamin premix 0.3 Calcium lactate23.2 Water to 100% wt

The product shows good satiety effects (may be consumed as a dilutedproduct) compared to the equivalent composition wherein the whey proteinhydrolysate is replaced by the same amount of cow's milk protein.

In examples 3 to 5 the whey protein hydrolysate may be replaced by thenon-hydrolysed whey protein according to the present invention.

1. Method of treating and/or preventing obesity or being overweight in/of a human subject, said method comprising administering to the human subject an edible composition comprising an effective amount of whey protein hydrolysate, to induce the cellular release of glucagon-like-peptides and cholecystokinins, said whey protein hydrolysate having a molecular weight profile as measured by SEC-HPLC of 30 to 45% greater than 10,000 Dalton, 7 to 12% in the range 5000 to 10,000 Dalton, 15 to 25% in the range 2000 to 5000 Dalton and 30-45% less than 2000 Dalton.
 2. The method according to claim 1, wherein the whey protein hydrolysate comprises hydrolysates of β-lactoglobulin, α-lactalbumin or a mixture thereof.
 3. The method according to claim 2, wherein the hydrolysates of β-lactoglobulin and α-lactalbumin are present in the edible composition in a weight ratio of from 5:1 to 1:5.
 4. The method according to claim 1, wherein the whey protein hydrolysate has a degree of hydrolysis in the range of from 1 to 20%.
 5. The method according to claim 1, wherein the edible composition is a food composition used in a weight loss or weight control plan.
 6. The method according to claim 1, wherein the edible composition comprises a meal replacement product.
 7. The method according to claim 1, wherein the edible composition is selected from the group consisting of a ready-to-drink liquid, a liquid produced from a soluble powdered product, a soup, a dessert, a bar, a cereal based or pasta based or noodle based product, and a powdered product. 